Incidental Mutation 'R0054:Snip1'
ID17167
Institutional Source Beutler Lab
Gene Symbol Snip1
Ensembl Gene ENSMUSG00000050213
Gene NameSmad nuclear interacting protein 1
Synonyms2410133M08Rik
MMRRC Submission 038348-MU
Accession Numbers

Ncbi RefSeq: NM_175246.4; MGI: 2156003

Is this an essential gene? Probably essential (E-score: 0.931) question?
Stock #R0054 (G1)
Quality Score
Status Validated
Chromosome4
Chromosomal Location125066672-125074042 bp(+) (GRCm38)
Type of Mutationnonsense
DNA Base Change (assembly) T to A at 125072840 bp
ZygosityHeterozygous
Amino Acid Change Tyrosine to Stop codon at position 354 (Y354*)
Ref Sequence ENSEMBL: ENSMUSP00000060721 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000052183]
Predicted Effect probably null
Transcript: ENSMUST00000052183
AA Change: Y354*
SMART Domains Protein: ENSMUSP00000060721
Gene: ENSMUSG00000050213
AA Change: Y354*

DomainStartEndE-ValueType
low complexity region 6 19 N/A INTRINSIC
low complexity region 42 56 N/A INTRINSIC
low complexity region 62 89 N/A INTRINSIC
low complexity region 132 146 N/A INTRINSIC
FHA 267 331 1.52e-14 SMART
low complexity region 370 378 N/A INTRINSIC
Predicted Effect noncoding transcript
Transcript: ENSMUST00000145733
Meta Mutation Damage Score 0.6228 question?
Coding Region Coverage
  • 1x: 88.8%
  • 3x: 85.6%
  • 10x: 76.3%
  • 20x: 59.9%
Validation Efficiency 96% (91/95)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a protein that contains a coiled-coil motif and C-terminal forkhead-associated (FHA) domain. The encoded protein functions as a transcriptional coactivator that increases c-Myc activity and inhibits transforming growth factor beta (TGF-beta) and nuclear factor kappa-B (NF-kB) signaling. The encoded protein also regulates the stability of cyclin D1 mRNA, and may play a role in cell proliferation and cancer progression. Mutations in this gene are a cause of psychomotor retardation, epilepsy, and craniofacial dysmorphism (PMRED). [provided by RefSeq, Mar 2012]
Allele List at MGI

All alleles(4) : Targeted(3) Gene trapped(1)

Other mutations in this stock
Total: 57 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abcc9 A G 6: 142,601,774 probably null Het
Apoa4 A G 9: 46,242,524 D141G probably benign Het
Arntl2 T G 6: 146,829,718 V507G probably benign Het
Atg9a T C 1: 75,184,499 Y701C probably damaging Het
Baz2b C T 2: 59,932,166 R922Q probably damaging Het
Brms1 T A 19: 5,046,699 C136* probably null Het
Ccdc180 T A 4: 45,890,900 V24E probably benign Het
Clec4f C T 6: 83,652,929 V216M probably benign Het
Cpd C G 11: 76,790,838 G1160R probably damaging Het
Creb5 A G 6: 53,447,657 M128V probably benign Het
Ddb2 G T 2: 91,234,820 Q87K probably benign Het
Defb41 A G 1: 18,251,247 Y48H probably damaging Het
Dido1 T C 2: 180,661,474 N1546D probably benign Het
Dmac1 A G 4: 75,278,100 V51A possibly damaging Het
Dnajb11 C T 16: 22,862,619 A49V probably damaging Het
Dnajc14 G A 10: 128,807,579 D457N probably damaging Het
Eif3a C A 19: 60,766,826 D973Y unknown Het
Farsb T A 1: 78,462,374 K395* probably null Het
Fem1b A G 9: 62,796,800 S393P probably damaging Het
Fsip2 A C 2: 82,986,955 N4344T possibly damaging Het
Gphn A G 12: 78,637,503 S558G probably damaging Het
Gpr142 C A 11: 114,798,929 H2Q probably benign Het
Grhpr T C 4: 44,988,915 probably benign Het
Grik3 C A 4: 125,623,575 N70K probably damaging Het
Gsap T A 5: 21,250,935 probably benign Het
Iars T A 13: 49,693,135 C237S probably damaging Het
Ighv1-9 A T 12: 114,583,982 F7L probably benign Het
Ints8 A G 4: 11,204,595 probably benign Het
Kcnj16 G T 11: 111,024,723 W70C probably damaging Het
Kpna6 T C 4: 129,657,458 M85V probably benign Het
Kri1 G A 9: 21,275,365 S447L probably damaging Het
Lrp1b A G 2: 40,742,817 V3528A probably benign Het
Lrrc46 A T 11: 97,038,779 L77Q probably damaging Het
Mrpl44 T C 1: 79,779,495 L219S probably damaging Het
Ms4a14 T C 19: 11,303,939 I418M probably benign Het
Myo7a T C 7: 98,065,698 D112G probably damaging Het
Ncoa3 A G 2: 166,055,178 T630A possibly damaging Het
Nsl1 T C 1: 191,082,184 L194P probably damaging Het
Olfr1037 T C 2: 86,085,361 K139E probably benign Het
Olfr205 T C 16: 59,329,065 Y148C possibly damaging Het
Pde4d A G 13: 109,740,421 S159G probably benign Het
Pi4ka T C 16: 17,325,114 R845G probably null Het
Pld1 A G 3: 28,095,884 probably benign Het
Psd T A 19: 46,323,342 I300F probably damaging Het
Ptprz1 T A 6: 22,986,196 W332R probably damaging Het
Rnf212 T A 5: 108,745,664 M70L possibly damaging Het
Sema4f A G 6: 82,919,693 probably benign Het
Sez6 C A 11: 77,953,873 T7K possibly damaging Het
Skint2 T C 4: 112,645,463 I290T probably benign Het
Slc5a3 T A 16: 92,077,634 I193N probably damaging Het
Tmco5 A G 2: 116,887,287 Y200C probably damaging Het
Tmem87b T A 2: 128,831,441 probably benign Het
Trim60 T C 8: 65,001,321 E92G probably benign Het
Ttn A T 2: 76,796,460 D13067E possibly damaging Het
Ufl1 A T 4: 25,269,087 I168N probably damaging Het
Zfp385c G A 11: 100,629,956 P293S probably benign Het
Zfp473 T A 7: 44,734,475 S144C probably damaging Het
Other mutations in Snip1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL02223:Snip1 APN 4 125072752 missense possibly damaging 0.66
R0054:Snip1 UTSW 4 125072840 nonsense probably null
R1163:Snip1 UTSW 4 125072820 missense probably damaging 1.00
R1735:Snip1 UTSW 4 125071201 missense probably benign 0.00
Protein Function and Prediction

Overexpression of Snip1 inhibits the transcriptional activation of Smad4 and NF-κB by blocking their interactions with CBP/p300 (1;2). Snip1 is involved in the cotranscriptional or posttranscriptional regulation of cyclin D1 mRNA stability (3). Snip1 also associates with c-Myc, a regulator of cell proliferation and transformation; Snip1 enhances the transcriptional activity of c-Myc by both stabilizing it against degradation and by bridging it to p300 (4). The Snip1 protein contains an N-terminal nuclear localization signal and a C-terminal forkhead-associated domain (1).  The N-terminus of Snip1 has been shown to interact with both the TGF-β family signaling protein Smad4 and the NF-κB transcription factor p65/RelA as well as the transcriptional coactivators CBP and p300 (1;2).

Expression/Localization

Northern blot analysis detected the ubiquitous expression of three transcripts (4.4, 2.4, and 1.5 kb); highest expression was in the heart and skeletal muscle (1).  Western blot detected protein expression of Snip1 in all mouse tissues examined (1). Immunohistochemistry determined that Snip1 localized to epithelial elements in rat kidney sections; in a mouse mammary cell line, Snip1 localized to the nucleus (1).

Background

A mutation in SNIP1 (an A to G transition at 1097; E366G) is linked to psychomotor retardation, epilepsy, and craniofacial dysmorphism [OMIM: 614501; (5)].

References
Posted On2013-01-20
Science WriterAnne Murray